Melanogenesis is caused when melanin production is increased in melanin pigment producing cells (hereinafter, referred to as ‘melanocytes’) within skin cells due to certain causes such as ultraviolet rays, and thereby a large amount of produced melanin is transferred to keratinocytes, and accumulated in an epidermis. Hyperpigmentation in skin, caused by melasma, freckle, melanogenesis following skin inflammation, senile plaque, etc, not only gives cosmetic inconvenience to the person concerned but also has a psychologically negative effect on him or her, causing inconvenience in social activities. Due to an increase of such a requirement, whitening cosmetics, medical supplies, etc. for preventing and improving hyperpigmentation have been marketed.
Whitening agents as cosmetics have been researched with a history of less than 10 years. As the standards of living of Asian people who prefer white skin advance, melanogenesis has been recognized as skin aging caused by ultraviolet rays. Thus, necessities of the whitening agents have been gradually increased. Since the 1990s, arbutin, kojic acid, vitamin C and derivatives thereof have been developed, and whitening cosmetics containing these have been marketed. However, their substantial clinical effects are unsatisfactory. As medical supplies for improving hyperpigmentation, hydroquinone, sulfure, azelaic acid, retinoic acid, etc. have been used, but these materials are highly irritative and toxic.
The early whitening agent development focused on the inhibition of tyrosine oxidation by tyrosinase, that is, the first step of a melanin pigment producing process. Thus, through in vitro experiment, the selection of tyrosinase deactivators was an important development means for whitening agents.
Especially, tyrosinase used in the experiment is derived from mushrooms, and shows considerable differences in characteristics with that derived from human. When whitening agents selected in the experiment are in actuality applied to a human body, problems such as skin penetration, cytotoxicity, or formulation stability are caused. Thus, they are insufficient in substantial clinical effect. However, materials found through such a process, such as arbutin, kojic acid, vitamin C, etc. have been widely used up to now.
Accordingly, it is urgently required to develop a material that can effectively reduce melanin expression without the above mentioned problems such as side effects or toxicity.
Melanoma is malignant tumor of melanocytes, that is, cells branched from a neural crest.
Melanoma is mainly found in a general skin area, but may also occur on other mucous membrane surfaces. When skin nevus seems to be darker, has a variable discoloration, is itching, becomes larger in size, or is accompanied with satellites, it can be doubtful about a malignant change of the skin nevus. Melanoma is unusual because it much more easily metastasizes than other types of cancers, and can spread to local or distal lymph nodes, or any main organ systems of a body. Besides skin, regions to which melanoma is the most frequently metastasized are lung, liver, brain and lymph node. Melanoma more frequently occurs in men, and is found in adults of all ages. According to American Cancer Society (ACS), during 2005 in US, 59,580 cases of melanoma occurred, and 7,770 people died from melanoma.
A test that was conducted using interferon and interleukin together with dacarbazine did not show clinical advantages in progressed melanoma, as compared to a therapy using dacarbazine alone. It was found that an immunotherapic agent used in combination with lymphokine-activated lymphocytes has no effect on improvement of a reaction rate, or lasting relief. DTIC (Dimethyl Triazeno Imidazole Carboxamide) is currently only one chemotherapeutic agent that has been approved for use in metastatic melanoma. In the treatment of metastatic melanoma, the efficacy of dacarbazine is highly dependent on a disease region. According to recent publications and abstracts (Journal of Clinical Oncology and ASCO annual meeting proceedings, 2004), the entire reaction rate on DTIC in actuality ranges from 5.5 to 6.8%, and this reaction is temporary (that is, 3 to 6 months). There is no evidence that this reaction has a certain effect on general survival of the patient.
Accordingly, it is urgently required to develop a novel material that can prevent or treat malignant melanoma by inhibiting hyperplasia of melanocytes.